[HTML][HTML] Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation

I Gandolfini, E Crespo, M Baweja, M Jarque… - PLoS …, 2018 - journals.plos.org
I Gandolfini, E Crespo, M Baweja, M Jarque, C Donadei, S Luque, N Montero, A Allesina…
PLoS One, 2018journals.plos.org
Donor-specific (d-sp) interferon gamma enzyme-linked immunosorbent spot (d-sp ELISPOT)
and Panel of reactive T-cell (PRT) ELISPOT assays have been developed to detect
alloreactive memory T (Tmem) cells in order to estimate the risk of acute rejection after
kidney transplantation. Adding IL15 to the PRT assay (PRT+ IL15) may uncover the
presence of pathogenic alloreactive CD28-Tmem. Face-to-face comparisons of these
assays have not been done yet. We performed pre-transplant d-sp ELISPOT and PRT …
Donor-specific (d-sp) interferon gamma enzyme-linked immunosorbent spot (d-sp ELISPOT) and Panel of reactive T-cell (PRT) ELISPOT assays have been developed to detect alloreactive memory T (Tmem) cells in order to estimate the risk of acute rejection after kidney transplantation. Adding IL15 to the PRT assay (PRT+IL15) may uncover the presence of pathogenic alloreactive CD28-Tmem. Face-to-face comparisons of these assays have not been done yet. We performed pre-transplant d-sp ELISPOT and PRT assays (±IL15, against six B-cell lines) in 168 consecutive kidney transplant recipients and evaluated the multivariable-adjusted associations with biopsy-proven acute rejection (BPAR), de novo donor-specific antibodies (DSA), and eGFR decline over a 48-month follow-up period. D-sp ELISPOT was positive in 81 (48%) subjects, while 71 (42%) and 81 (48%) subjects displayed positive PRT and PRT+IL15, respectively. Their median [interquartile range] numerical test result was 23 [6–65], 18 [8–37], and 26 [10–45] spots/3x105 PBMCs, respectively. The number of PRT spots were weakly correlated with those of d-sp ELISPOT, but highly correlated with PRT+IL15 (rho = 0.96, P<0.001). d-sp ELISPOT, but not PRT (±IL15) was independently associated with BPAR (adjusted Odds Ratio of BPAR associated with d-sp ELISPOT positivity: 4.20 [95%CI: 1.06 to 21.73; P = 0.041]). Unlike d-sp ELISPOT, median PRT and PRT+IL15 were independently associated with higher Δ3-48month eGFR decline post-transplantation (for both assays, about -3mL/min/1.73m2 per one standard deviation unit increase in the spot number). Pre-transplant T-cell immune-monitoring using d-sp ELISPOT and PRT assays identifies kidney transplant candidates at high risk of BPAR and worse kidney allograft progression.
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